title: MiR-492 impairs the angiogenic potential of endothelial cells.
abstract: Endothelial cells growing in high glucose-containing medium show reduced cell proliferation and in vitro angiogenesis. Evidence suggests that the molecular pathways leading to these cellular responses are controlled by microRNAs, endogenous post-transcriptional regulators of gene expression. To identify the microRNAs and their targeted genes involved in the glucose responses, we performed the miRNA signature of Human Umbelical Vein Endothelial Cells (HUVECs) exposed and unexposed to high glucose. Among differentially expressed microRNAs, we analysed miR-492 and showed that its overexpression was able to reduce proliferation, migration and tube formation of HUVEC. These effects were accompanied by the down-regulation of eNOS, a key regulator of the endothelial cell function. We showed that eNOS was indirectly down-regulated by miR-492 and we discovered that miR-492 was able to bind mRNAs involved in proliferation, migration, tube formation and regulation of eNOS activity and expression. Moreover, we found that miR-492 decreased VEGF expression in HUVEC and impaired in vivo angiogenesis in a tumour xenograft model, suggesting a role also in modulating the secretion of pro-angiogenic factors. Taken together, the data indicate that miR-492 exerts a potent anti-angiogenic activity in endothelial cells and therefore miR-492 seems a promising tool for anti-angiogenic therapy.
authors.affiliation: Laboratory of Molecular and Gene Therapy, Institute of Clinical Physiology, CNR, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Patella
authors.forename: Eleonora
authors.initials: E
authors.lastname: Leucci
authors.forename: Monica
authors.initials: M
authors.lastname: Evangelista
authors.forename: Brian
authors.initials: B
authors.lastname: Parker
authors.forename: Jiayu
authors.initials: J
authors.lastname: Wen
authors.forename: Alberto
authors.initials: A
authors.lastname: Mercatanti
authors.forename: Milena
authors.initials: M
authors.lastname: Rizzo
authors.forename: Elena
authors.initials: E
authors.lastname: Chiavacci
authors.forename: Anders H
authors.initials: AH
authors.lastname: Lund
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rainaldi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D057075:Enzyme Assays; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C558125:MIRN492 microRNA, human; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D008156:Luciferases; D052250:Nitric Oxide Synthase Type III; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human
keywords: eNOS; endothelial cell; microRNA